Professor M. Wills

Warwick University Department of Chemistry Year 1, Course CH158: Foundations of Chemistry Section A3; Basics of Organic Chemistry Professor Martin Wills m.wills@warwick.ac.uk Important: Pleasebear in mind that organic chemistry ‘builds upon itself’ – you must make sure that you fully understand the earlier concepts before you move on to more challenging work. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Nomenclature of Organic Compounds IUPAC has defined systematic rules for naming organic compounds. These will have already been covered in detail at A-level and will only be mentioned briefly here. The naming system (and the resulting names) can become very long with complex molecules, therefore this section will be restricted to simple compounds. The IUPAC naming system involves the following components: - Identification of major chain or ring - Side chains and functional groups are added as appropriate, in alphabetical order. - The sums of numbers for substituents are minimised Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Nomenclature of Organic Compounds Examples: is 3-methyloctane, not 5-methyloctane Is 5-(1’-methylethyl)-2,2,4-trimethyloctane Is 4,5-diethyl-2,2-dimethylheptane It is NOT 3,4-diethyl-6,6-dimethylheptane! Butan-2-ol 2-chlorobutane Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Nomenclature of Organic Compounds Many common names persist in organic chemistry, despite IUPAC rules, e.g. Compound ‘common’ name IUPAC name Acetone Propanone Formaldehyde Methanal Acetic acid Ethanoic acid Dimethylether Methoxymethane Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Substitution level and functional groups The ‘substitution level’ of a carbon atom in an organic compound is determined by the number of attached hydrogen atoms: The rules differ for certain functional compounds e.g. alcohols: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Substitution level and functional groups In the case of AMINES, the rules are different: Aromatic compounds: substitution position relative to group ‘X’ Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Substitution level and functional groups Functional groups will be dealt with as they arise, however the following should be committed to memory: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Line drawing - the standard from this point in the course Line drawing represents an abbreviated ‘shorthand representation of organic structures: The rules are simple- Structures are written as a series of interconnected lines where each apex is the position of a carbon atom. Heteroatoms (i.e. not H or C) are shown. H atoms are not shown with the exception of those on heteroatoms. N.b. in some cases the H atom of an aldehyde may be illustrated Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Oxidation level This is a useful tool for the understanding of organic reactions. It is slightly different to the system used for the oxidation level of cations and anions. In some cases it is obvious that a reaction is an oxidation or reduction, in other cases they are not, for example: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Oxidation level To assign oxidation number (Nox), identify each each carbon atom that changes and assign oxidation numbers as follows: a) For each attached H assign ‘-1’. b) For each attached heteroatom (O, N, S, Br, Cl, F, I etc.) assign ‘+1’. c) Double or triple bonds to heteroatoms count double or triple respectively. Then sum them for each molecule. A change of ‘+2’ indicates an oxidation. A change of ‘-2’ indicates a reduction. note + 2 or -2 is the typical change in oxidation level. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Molecular Stability - covalent vs ionic bonding Many factors dictate the stability of atoms and ions. Hydrogen atoms gain stability if there are two electrons in their electron shell. For first and second row elements, significant stability is derived from an outer electronic configuration with 8 electrons. Atoms can achieve this by i) gaining or losing electrons or ii) sharing them. In the periodic table: The simplest example is where two hydrogen atoms combine to form H2, with a covalent bond between the atoms: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Molecular Stability - covalent vs ionic bonding Examples of covalent compounds: (nb the three dimensional shapes of the molecules will be discussed in a later section) Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Molecular Stability - covalent vs ionic bonding Examples of covalent compounds: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D. Linear combination of atomic orbital (LCAO) model. • Always remember that atomic orbitals (in atoms) combine to give molecular ones (in molecules - which is obvious) but there are some rules: • n atomic orbitals form n molecular orbitals. • The combination of atomic orbitals leads to the formation of a combination of bonding, nonbonding and antibonding orbitals. • In a stable molecule, the antibonding orbitals are empty, which is why it is stable! • e.g. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D. Linear combination of atomic orbital (LCAO) model. This is how the energy of the orbitals would be depicted: Always bear this in mind when thinking about molecular orbital structure. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Bond Polarity Covalency suggests equal sharing, but this is rarely the case because atoms differ in their inherent ability to stabilise negative charge, I.e. their ‘electronegativity. Electronegativity increases in the direction of the arrows shown below (for the first two rows of the periodic table): Pauling scale of electronegativity allows a quantitative comparison: e.g. H (2.1), C (2.5), N (3.0), O (3.5), F (4.0), Cl (3.0), Br (2.8), I (2.5) etc. As a result, most heteroatoms (X) are more electronegative that carbon and C-X bonds are polarised so that there is a partial positive charge on the carbon atom. See next page for examples Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Bond Polarity Examples of covalent bonds which contain a dipole: A few elements (notably metals) are less electronegative than C. As a result the dipole is reversed: This polarity effect is sometimes referred to as the INDUCTIVE effect, and operates through sigma bonds in molecules (see a later section). Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Formal Charge Formal charge is a method for assigning charge to individual atoms in molecules. Although it does not always give a ‘perfect’ picture of true charge distribution, it is very helpful when reaction mechanisms are being illustrated. The definition of formal charge on a given (row 1 or 2) atom is as follows: Formal charge on atom X (FC (X)) = (‘atomic group number’ of the atom* – ignore transition metals when counting!)-(number of bonds to the atom)- 2(number of lone pairs on the atom). (You may see a slightly different version of the equation in other places). Example: N.b - use a atomic group number of ‘1’ for hydrogen. * i.e. count from 1 to 8 across the row. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Formal Charge Further examples: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Acidity of organic compounds Acidity is a measure of the ability of a compound to ionise to a proton and a negatively charged counterion. Group. Organic compounds are not very acidic compared to strong mineral acids, however some are stronger acids than others. Let’s put this into context. The relative acidity in aqueous solution of a compound is defined by its pKa. This is a measure of the inherent ability of any compound to lose a proton in an equilibrium process: Think about this for a second… If HXR is a strong acid, the equilibrium will be over to the right hand side. Ka will be high and pKa will be a low number (possibly even negative). Carboxylic acids, the strongest organic acids, have a pKa of around 5. If HXR is a weak acid he the equilibrium with be over to the left hand side, Ka will be low and the pKa will be quite high. Alkanes (CnH2n+2) are very reluctant to lose a proton and are weak acids. The pKa of an alkane is around 40. Most organic compounds have pKas between these extremes. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course, Section A3; Acidity of organic compounds Nb - a related scale, pH, is a measure of the amount of protons in a solution at any moment. pH is defined as -log [H+]. Here are a few more examples of pKa values of organic compounds. Remember that each unit of pKa represents a tenfold change in acidity. Some examples (no. relates to circled proton) are given below: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D. Rehybridisation and VSEPR: The three-dimensional structure of organic compounds often influences their properties and reactivity. Each carbon atom in an organic molecule can be linked to four, three or two other groups. In each case the orbital structure and three-dimension shape around that carbon atom is different In the case of a carbon atom attached to four other groups by single bonds, the single 2s and the three 2p orbitals gain stability by mixing (rehybridisation) to form four sp3 orbitals. These are all arranged at mutual 109.5 degree angles to each other and define a tetrahedral shape: A tetrahedral shape is favoured because this maximises the distance between the filled orbitals, which contain negatively charged electrons, and therefore repel each other. This is known as the ‘valence shell electron pair repulsion’ (or VSEPR), and often dominates the shape of molecules. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D. The VSEPR model for the structure of molecules also explains why molecules such as ammonia and water are not flat or linear respectively. Their structures are ‘bent’ because of repulsion effect of the electrons in the lone pairs (which are in sp3 orbitals). Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D. Some things to be aware of: i) Symmetrical, tetrahedral, compounds have no overall dipole: ii) Molecules which are electron deficient, such as borane (BH3), retain a trigonal shape. Why? – Well, without an electron pair, there is nothing to repel with!!! Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D In the case of a carbon atom attached to three other groups (by two single bonds and one double bond) the single 2s and two2p orbitals mix (rehybridise) to form three sp2 orbitals. These are all arranged at mutual 120 degree angles to each other and define a trigonal shape, the remaining p orbital projects out of the plane of the three sp2 orbitals and overlaps with an identical orbital on an adjacent atom to form the double bond: The resulting structure is rigid and cannot rotate about the C=C bond without breakage of the bond between the p-orbitals (the p bond). Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D In the case of a carbon atom attached to two other groups (by one single bonds and one triple bond) the single 2s and one 2p orbitals mix (rehybridise) to form two sporbitals. These are all arranged at mutual 180 degree angles to each other and define a linear shape, the remaining p orbitals projecting out from the sporbital to overlap with identical orbitals on an adjacent atom to form the triple bond: Rehybridisation of orbitals of this type is not limited to carbon, of course. Many other row 1 and 2 atoms (notably N) can rehybridise within organic molecules. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D Conformation and configuration Configuration is a fixed stereochemical property of compounds. Unlike conformation, a change in configuration requires bonds to be broken and formed. Any molecule has a limited number of configurations in which it can exist. Alkenes can exist in two configurations, for example but-2-ene may have the terminal methyl groups in a trans (across from each other) or cis (on the same side) position: Changing trans butadiene into cis- butadiene (or vice versa) requires the breaking, and subsequent reforming, of the p bond. This is a high- energy process and does not take place at room temperature. At room temperature, but-2-ene (and other alkenes) can be physically separated into the two pure isomers. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration The configuration of an alkene can be obvious in some cases (such as but-2-ene) however in others it is not, for example is the molecule below a cis or trans alkene? In order to provide an unambiguous means for assigning configuration to alkenes (and also to chiral centres as you will see later), organic chemists have adopted the ‘Cahn-Ingold-Prelog’ (CIP) rules for configurational assignment. These are simple to use - first one assigns a ‘priority’ to each group attached to each carbon atom at each end of the alkene. I will describe to priority rules in the next slide. We then define the alkene as either Z (from the German zusammen, together) or E (from the German entgegen, across): Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D Conformation and configuration The CIP priority rules are defined as follows, in their own order of priority: a) Atoms of higher atomic number have priority: b) When the attached atoms are identical on each side, isotopes of higher mass have priority Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration The CIP priority rules are defined as follows, in their own order of priority: a) When the atoms and isotopes attached on each side are identical, move out until a point of difference is encountered and apply the following rules: a) Priority goes to the group with the element of highest atomic number at the point of difference. b) Priority goes to the group with the highest sum of atomic numbers if the atoms are of the same types at the point of difference. In the example below, the point of difference on the right hand side is two carbons away from the alkene carbon atom Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration This is how I worked out the last example (right hand side only): There is one more rule: d) In the case of double and triple bonds, ‘dummy’ atoms should be added and counted in the determination of priority. See next slide. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration Here is an example of the determination of configuration for an alkene attached to a double bond: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration CIP priority rules are also applied to the determination of configuration at chiral centres (a chiral molecule is one which is not superimposable on its mirror image, rather like your hands). The simplest form of a chiral centre is one with a carbon atom attached to four different groups. E.g. To assign a configuration to a chiral molecule such as the one shown above we first assign CIP priorities to all four groups using the same rules: e.g. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration We then view the molecule, with the assigned priorities, along the C-4 bond (with the 4 behind the central carbon atom. Finally, draw an arrow from atom with priority 1 to priority 2 to priority 3 in turn: In this case the arrow is clockwise; this is therefore referred to as a R isomer (R comes from the Latin rectus, for ‘right’). Isomers of this type are sometimes called ‘enantiomers’. The mirror image of the molecule above is the S enantiomer (from the Latin sinister for ‘left’) Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration Here are a couple of examples - can you see the derivation of the configuration? One carbon atom makes all the difference! Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration This is quite important – please read it. Some other conventions are used to defined the configuration at chiral centres e.g. l - molecule with a negative optical rotation (from the Greek for levorotatory; left) d - molecule with a positive optical rotation (from the Greek for dextrarotatory; right) The D/L notation ( a very old convention) is derived from the signs of optical rotation of R and S glyceraldehyde respectively: The trivial convention for the absolute configurations of sugars derives from the D/L notation above. D-glucose is the natural enantiomer (costs £20/kg) whilst L-glucose is very rare (£31/g!). Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration Amino acids are classified into L- (natural) and D- (unnatural) Most L-amino acids are of S- configuration. Despite all the different notations, R and S is the one YOU should learn how to use. Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Year 1 Foundation course section A3; Molecules in 3D - Conformation and configuration The two mirror-images of chiral compounds can have dramatically different physical properties. That is because we ourselves are made up of molecules of one ‘handedness’. Try assigning R/S to these: Professor M. Wills CH158 Year 1 A3 Basics of Organic Chemistry

Professor M. Wills